A COMMENTARY ON ANALYSIS OF SURVIVAL AMONG ADULTS WITH EARLY-ONSET COLORECTAL CANCER

Despite widespread implementation of colorectal cancer (CRC) screening, CRC continues to be in the top five leading causes of cancer-related deaths in the United States.¹ The article by Cheng et al. examines the survival benefit of early-onset (<50 years) CRC compared to subjects ages 51–55.² The authors find a modest survival benefit for early-onset CRC patients, particularly those between 35–39 years of age. These results offer support for effectiveness of treatment in patients diagnosed with CRC at young ages; however, they must be interpreted within the context of epidemiological and biological factors.

Over the last 20 years, overall CRC incidence rates have been down trending.³ The study by Cheng et al demonstrates a spike in CRC diagnoses at age 50, particularly in early stage cancer, likely related to age-based screening.² CRC-related death rates declined by 34% for patients ≥50 from 2000 to 2013.³ However, rates of CRC diagnoses in young adults <50 have increased by 22% with a 13% increase in CRC-related mortality from 2000 to 2013.³ The United States Preventive Services Task Force (USPSTF) recently lowered the CRC screening age to 45 from 50 (B grade recommendation) in their 2020 draft recommendation statement.⁴ This recommendation was based on modeling analyses suggesting more life-years gained, fewer CRC-related deaths, and a favorable balance of benefit and harms when screening begins at age 45.⁴ Cheng et al. found survival benefits within early-onset patients that varied by age and stage. Patients aged 35–39 experienced a modest survival benefit compared to patients aged 51–55 that was largely limited to patients diagnosed at stage I and II.² While these results do not suggest that screening start younger than 45, they do support the benefit of early detection in young patients.

While Cheng et al. found a modest survival benefit for early-onset CRC patients, particularly for those diagnosed with early-stage cancer, there are several factors to consider when interpreting these results. First, CRC remains rare in the population under 45 years, at 25 new cases diagnosed per 100,000 people per year. ⁵Those with early-onset CRC typically present with higher risk pathology, and more advanced or distal disease compared to patients older than 50; yet also have higher cancer-specific survival.⁶ This may be partially attributed to fewer comorbidities. Additionally, patients with early onset CRC tend to undergo more aggressive management, including greater lymph node harvest (>12 lymph nodes examined), and to undergo systemic therapy within 6 months of diagnosis.⁶ While there is no difference in management recommendations between early-onset and late-onset CRC, the differences in clinical practice, and thus potentially survival, may reflect patient and provider age-related factors.

While there is significant evidence supporting the benefits of CRC screening in the population over 45,³ it is not without risk. USPSTF recommended modalities for CRC screening include stool-based studies, flexible sigmoidoscopy, colonoscopy, and CT colonography, with most serious harms (bleeding or perforation) associated with colonoscopies and sigmoidoscopies. Based on draft modeling, screening from ages 45 to 75 years via one of the aforementioned modalities would result in 1,535 to 4,248 colonoscopy procedures, and 10 to 16 complications over the lifetime of 1,000 screened patients.⁴ While the expected complication number is relatively small, it is not negligible and the use of screening should be reserved for patients in the recommended age category, where benefit outweighs risk. From 2014–2018, less than 7% of all new CRC diagnoses were in patients <45.¹ Given this fairly low incidence rate, there has been little to no evidence to support screening asymptomatic patients <45. However, a full diagnostic evaluation is warranted for patients of any age who present with signs and symptoms concerning for CRC, which is reiterated by the results of the report by Cheng, et al.²

In addition to the benefits and risks, the costs of age-based population screening must be considered. As Cheng, et al report, the survival benefits of early-onset CRC were modest and therefore a thorough cost-effectiveness analysis is essential to understand the economic implications of expanding CRC screening.² In a cost-effectiveness analysis, the costs of expanding screening protocols for patients younger than 45 must be weighed with the added life-years or deaths prevented. There is currently no evidence of benefits of lowering the screening asymptomatic patients under 45. Furthermore, the costs and outcomes of risks associated with screening, such as those mentioned above, must be included in the analysis. The USPSTF deliberately does not consider the costs of a preventive intervention, to provide focus on the clinical effectiveness of interventions they recommend. Nonetheless, costs are a critical concern for insurers, health care providers, and consumers, particularly in the current environment of rising cancer care costs.⁷

CRC screening for patients ≥50 has been well studied and proven effective in lowering the overall observed incidence of CRC. While CRC diagnoses and CRC-related deaths have been trending up in patient ≤50 years of age, one would expect this trend to slow as the new screening age of 45 years or older is implemented. CRC diagnoses in patients <45 continue to represent a small percentage of all CRC diagnoses but the findings by Cheng et al.² provide optimism about treatment outcomes in these patients. More information is needed to understand how the updated USPSTF CRC screening recommendations will impact mortality in patients screened between the ages of 45 and 50.